Continuous Manufacturing for Drug Product
Continuous manufacturing for drug product offers significant advantages that save development time and assure faster commercial supply.
In recent years continuous manufacturing has been gaining traction as a solution to the increasing pressure on drug manufacturers to reduce development time and costs (by using the same equipment for development and commercial-scale production, and less API), and to assure robust supply of quality product (through enhanced process control strategies). Continuous manufacturing is therefore well suited for the production of precision medicines and those with breakthrough therapy designations.
Hovione’s Plan for Continuous Manufacturing?
A state-of-the-art facility for continuous manufacturing of drug product will be installed in Hovione New Jersey’ site, expected to be operational by the end of 2017. The facility will allow the continuous production of tablets by means of direct compression, dry granulation, or wet granulations modes. Continuous steps will include blending, wet and dry granulation, fluid bed drying, tableting, and coating operations. An enhanced control strategy is assured by the use of Process Analytical Technologies (PAT) at multiple points, embedded in a multi-layered control system. Real-time-release testing (RTRt), and the necessary material traceability, is assured through appropriate use of process instrumentation, PAT, and modeling.
Process development is made at the same scale as commercial supply and follows a Quality-by-Design (QbD) approach. The use of PAT and an advanced control system results in meaningful data that can be used to better understand the relation between the desired quality attributes and both process parameters and raw material attributes; richer Design Spaces are thus obtained.
Faster clinical and commercial supply
As development is made at the same or similar scale of commercial supply, scale-up is eliminated from the workflow, as well as the risks commonly associated with it. For instance, avoiding formulation changes at later stages of development to accommodate higher scale equipment. Additionally, there are important API savings resulting from not having to conduct scale-up studies. Besides the lower risk, eliminating scale-up will decrease the time needed to reach commercial supply.
By its inherent features, continuous manufacturing allows going from powder to tablet in a matter of hours, instead of days or weeks. The one-continuous-operation and one-location production has important implications when assuring the faster supply of clinical materials, thus contributing to overall reduction in development time.
Higher quality and better consistency
Operation in continuous typically reflects in more robust processes, as instead of dealing with transient states, the control system needs only to assure steady-state. In addition, the online monitoring and control assured by the use of PAT, modeling and an advance control system, results in less variability and thus delivering more consistent product.
The use of online measuring of process parameters and quality attributes ensures richer data, i.e., higher number points of more meaningful data, making use of lower quantities of API. By means of adequate multivariate data analysis procedures and through the use of data-supported statistical and mechanistic modeling, relations between process inputs (raw materials attributes, process parameters) and process outputs (critical quality attributes) are easier to establish. Consequently, filing can be streamlined as a consequence of clearer evidences for process and product quality consistency.